Adenike Okunlola

Microbead design for sustained drug release using four natural gums

Four natural gums, namely albizia, cissus, irvingia and khaya gums have been characterized and evaluated as polymers for the formulation of microbeads for controlled delivery of diclofenac sodium. The natural gums were characterized for their material properties using standard methods. Diclofenac microbeads were prepared by ionotropic gelation using gel blends of the natural gums and sodium alginate at different ratios and zinc chloride solution (10%w/v) as the crosslinking agent. The microbeads were assessed using SEM, swelling characteristics, drug entrapment efficiencies and release properties. Data obtained from in vitro dissolution studies were fitted to various kinetic equations to determine the kinetics and mechanisms of drug release, and the similarity factor, f2, was used to compare the different formulations. The results showed that the natural gum polymers varied considerably in their material properties. Spherical and discrete microbeads with particle size of 1.48-2.41 μm were obtained with entrapment efficiencies of 44.0-71.3%w/w. Drug release was found to depend on the type and concentration of polymer gum used with formulations containing gum:alginate ratio of 3:1 showing the highest dissolution times. Controlled release of diclofenac was obtained over for 5h. Drug release from the beads containing the polymer blends of the four gums and sodium alginate fitted the Korsmeyer-Peppas model which appeared to be dependent on the nature of natural gum in the polymer blend while the beads containing alginate alone fitted the Hopfenberg model. Beads containing albizia and cissus had comparable release profiles to those containing khaya (f2>50). The results suggest that the natural gums could be potentially useful for the formulation controlled release microbeads.

Characterization and evaluation of acid-modified starch of Dioscorea oppositifolia (Chinese yam) as a binder in chloroquine phosphate tablets

Amido de inhame chines (Dioscorea oppositifolia), modificado por meio de hidrolise acida, foi caracterizado e avaliado como aglutinante em formulacoes de comprimidos de fosfato de cloroquina, em comparacao com o amido nativo. Determinaram-se as propriedades fisico-quimicas e de compressao (utilizando medidas de densidade e as equacoes de Heckel e Kawakita). Os efeitos quantitativos do amido modificado como ligante sobre as propriedades mecânicas e de liberacao de fosfato de cloroquina foram analisados por meio de um planejamento fatorial completo 23. Tomaram-se a natureza (X1), a concentracao de amido (X2) e a fracao de empacotamento (X3) como variaveis independentes e relacao forca de compressao-friabilidade (RFCE), tempo de desintegracao (DT) e tempo de dissolucao (t80), como variaveis dependentes. O amido de inhame chines modificado mostrou reducao marcante (p<0,05) no teor de amilose e da viscosidade, mas aumento no inchamento e nas propriedades de ligacao de agua. O amido modificado teve inicio rapido e maior quantidade de fluxo plastico. A alteracao do aglomerante da forma nativa para a modificada com acido conduziu a aumento significativo (p <0,05) em CSFR e DT, mas diminuicao da t80. O aumento da concentracao do aglutinante e da fracao de empacotamento deu origem a resultados semelhantes apenas para RFCE e DT. Os resultados sugerem que os amidos modificados com acido do inhame chines podem ser mais uteis como aglutinantes de comprimidos, quando se necessitam de forca de ligacao alta e de dissolucao rapida..

Evaluation of freeze-dried pregelatinized Chinese yam (Dioscorea oppositifolia) starch as a polymer in floating gastroretentive metformin microbeads

Pregelatinized Chinese yam (Dioscorea oppositifolia) starch has been evaluated as a polymer for the formulation of floating gastroretentive beads for the controlled delivery of metformin hydrochloride. Floating microbeads were prepared by the ionotropic gelation method using a blend of modified Chinese yam starch and sodium alginate at different ratios. Sodium bicarbonate was added as a gas-generating agent. The floating microbeads were characterized by SEM, DSC, FTIR analyses and the drug entrapment efficiency and floating ability was evaluated. Drug release was investigated using in vitro dissolution test and the results were fitted to various kinetic models to determine the mechanism(s) of release. Spherical, discrete and free flowing microbeads were obtained from the modified starch-alginate blends. Minimum lag time (

Design of bilayer tablets using modified Dioscorea starches as novel excipients for immediate and sustained release of aceclofenac sodium

Bilayer tablets of aceclofenac sodium were developed using carboxymethylated white yam (Dioscorea rotundata) starch (CWY) for a fast release layer (2.5, 5.0, and 7.5% w/w), and acid-hydrolyzed bitter yam (Dioscorea dumetorum) starch (ABY) for a sustaining layer (27% w/w). Sodium starch glycolate (SSG) and hydroxypropyl methyl cellulose (HPMC) were used as standards. The starches were characterized using Fourier Transform Infrared spectroscopy (FT-IR), particle size, swelling power, densities and flow analyses. Mechanical properties of the tablets were evaluated using crushing strength and friability while release properties were evaluated using disintegration and dissolution times. Distinctive fingerprint differences between the native and modified starches were revealed by FT-IR. Carboxymethylation produced starches of significantly (p < 0.05) higher swelling and flow properties while acid-modification produced starches of higher compressibility. Bilayer tablets containing ABY had significantly higher crushing strength and lower friability values (p < 0.05) than those containing HPMC. Crushing strength increased while friability values decreased with increase in CWY. Generally tablets containing the modified Dioscorea starches gave faster (p < 0.05) disintegration times and produced an initial burst release to provide the loading dose of the drug from the immediate-release layer followed by sustained release (300 ± 7.56–450 ± 11.55 min). The correlation coefficient (R2) and chi-square (χ2) test were employed as error analysis methods to determine the best-fitting drug release kinetic equations. In vitro dissolution kinetics generally followed the Higuchi and Hixson-Crowell models via a non-Fickian diffusion-controlled release. Carboxymethylated white yam starch and acid-modified bitter yam starch could serve as cheaper alternative excipients in bilayer tablet formulations for immediate and sustained release of drugs respectively, particularly where high mechanical strength is required.

Design of cissus–alginate microbeads revealing mucoprotection properties in anti-inflammatory therapy

Cissus gum has been employed as polymer with sodium alginate in the formulation of diclofenac microbeads and the in vivo mucoprotective properties of the polymer in anti-inflammatory therapy assessed in rats with carrageenan-induced paw edema in comparison to diclofenac powder and commercial diclofenac tablet. A full 2(3) factorial experimental design has been used to investigate the influence of concentration of cissus gum (X1); concentration of calcium acetate (X2) and stirring speed (X3) on properties of the microbeads. Optimized small discrete microbeads with size of 1.22±0.10 mm, entrapment efficiency of 84.6% and t80 of 15.2±3.5 h were obtained at ratio of cissus gum:alginate (1:1), low concentration of calcium acetate (5% w/v) and high stirring speed (400 rpm). In vivo studies showed that the ranking of percent inhibition of inflammation after 3h was diclofenac powder>commercial tablet=cissus>alginate. Histological damage score and parietal cell density were lower while crypt depth and mucosal width were significantly higher (p<0.05) in the groups administered with the diclofenac microbeads than those administered with diclofenac powder and commercial tablet, suggesting the mucoprotective property of the gum. Thus, cissus gum could be suitable as polymer in the formulation of non-steroidal anti-inflammatory drugs ensuring sustained release while reducing gastric side effects.